A MAFG-lncRNA axis links systemic nutrient abundance to hepatic glucose metabolism

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Standard

A MAFG-lncRNA axis links systemic nutrient abundance to hepatic glucose metabolism. / Pradas-Juni, Marta; Hansmeier, Nils R; Link, Jenny C; Schmidt, Elena; Larsen, Bjørk Ditlev; Klemm, Paul; Meola, Nicola; Topel, Hande; Loureiro, Rute; Dhaouadi, Ines; Kiefer, Christoph A; Schwarzer, Robin; Khani, Sajjad; Oliverio, Matteo; Awazawa, Motoharu; Frommolt, Peter; Heeren, Joerg; Scheja, Ludger; Heine, Markus; Dieterich, Christoph; Büning, Hildegard; Yang, Ling; Cao, Haiming; Jesus, Dario F De; Kulkarni, Rohit N; Zevnik, Branko; Tröder, Simon E; Knippschild, Uwe; Edwards, Peter A; Lee, Richard G; Yamamoto, Masayuki; Ulitsky, Igor; Fernandez-Rebollo, Eduardo; Vallim, Thomas Q de Aguiar; Kornfeld, Jan-Wilhelm.

In: Nature Communications, Vol. 11, 644, 2020.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Pradas-Juni, M, Hansmeier, NR, Link, JC, Schmidt, E, Larsen, BD, Klemm, P, Meola, N, Topel, H, Loureiro, R, Dhaouadi, I, Kiefer, CA, Schwarzer, R, Khani, S, Oliverio, M, Awazawa, M, Frommolt, P, Heeren, J, Scheja, L, Heine, M, Dieterich, C, Büning, H, Yang, L, Cao, H, Jesus, DFD, Kulkarni, RN, Zevnik, B, Tröder, SE, Knippschild, U, Edwards, PA, Lee, RG, Yamamoto, M, Ulitsky, I, Fernandez-Rebollo, E, Vallim, TQDA & Kornfeld, J-W 2020, 'A MAFG-lncRNA axis links systemic nutrient abundance to hepatic glucose metabolism', Nature Communications, vol. 11, 644. https://doi.org/10.1038/s41467-020-14323-y

APA

Pradas-Juni, M., Hansmeier, N. R., Link, J. C., Schmidt, E., Larsen, B. D., Klemm, P., Meola, N., Topel, H., Loureiro, R., Dhaouadi, I., Kiefer, C. A., Schwarzer, R., Khani, S., Oliverio, M., Awazawa, M., Frommolt, P., Heeren, J., Scheja, L., Heine, M., ... Kornfeld, J-W. (2020). A MAFG-lncRNA axis links systemic nutrient abundance to hepatic glucose metabolism. Nature Communications, 11, [644]. https://doi.org/10.1038/s41467-020-14323-y

Vancouver

Pradas-Juni M, Hansmeier NR, Link JC, Schmidt E, Larsen BD, Klemm P et al. A MAFG-lncRNA axis links systemic nutrient abundance to hepatic glucose metabolism. Nature Communications. 2020;11. 644. https://doi.org/10.1038/s41467-020-14323-y

Author

Pradas-Juni, Marta ; Hansmeier, Nils R ; Link, Jenny C ; Schmidt, Elena ; Larsen, Bjørk Ditlev ; Klemm, Paul ; Meola, Nicola ; Topel, Hande ; Loureiro, Rute ; Dhaouadi, Ines ; Kiefer, Christoph A ; Schwarzer, Robin ; Khani, Sajjad ; Oliverio, Matteo ; Awazawa, Motoharu ; Frommolt, Peter ; Heeren, Joerg ; Scheja, Ludger ; Heine, Markus ; Dieterich, Christoph ; Büning, Hildegard ; Yang, Ling ; Cao, Haiming ; Jesus, Dario F De ; Kulkarni, Rohit N ; Zevnik, Branko ; Tröder, Simon E ; Knippschild, Uwe ; Edwards, Peter A ; Lee, Richard G ; Yamamoto, Masayuki ; Ulitsky, Igor ; Fernandez-Rebollo, Eduardo ; Vallim, Thomas Q de Aguiar ; Kornfeld, Jan-Wilhelm. / A MAFG-lncRNA axis links systemic nutrient abundance to hepatic glucose metabolism. In: Nature Communications. 2020 ; Vol. 11.

Bibtex

@article{7df3d6893adf4718b57d90a2a21d1ec3,
title = "A MAFG-lncRNA axis links systemic nutrient abundance to hepatic glucose metabolism",
abstract = "Obesity and type 2 diabetes mellitus are global emergencies and long noncoding RNAs (lncRNAs) are regulatory transcripts with elusive functions in metabolism. Here we show that a high fraction of lncRNAs, but not protein-coding mRNAs, are repressed during diet-induced obesity (DIO) and refeeding, whilst nutrient deprivation induced lncRNAs in mouse liver. Similarly, lncRNAs are lost in diabetic humans. LncRNA promoter analyses, global cistrome and gain-of-function analyses confirm that increased MAFG signaling during DIO curbs lncRNA expression. Silencing Mafg in mouse hepatocytes and obese mice elicits a fasting-like gene expression profile, improves glucose metabolism, de-represses lncRNAs and impairs mammalian target of rapamycin (mTOR) activation. We find that obesity-repressed LincIRS2 is controlled by MAFG and observe that genetic and RNAi-mediated LincIRS2 loss causes elevated blood glucose, insulin resistance and aberrant glucose output in lean mice. Taken together, we identify a MAFG-lncRNA axis controlling hepatic glucose metabolism in health and metabolic disease.",
keywords = "Aged, Animals, Diabetes Mellitus, Type 2/genetics, Glucose/metabolism, Humans, Liver/metabolism, MafG Transcription Factor/genetics, Male, Mice, Middle Aged, Obesity/genetics, RNA, Long Noncoding/genetics, RNA, Messenger/genetics, Repressor Proteins/genetics, TOR Serine-Threonine Kinases/genetics",
author = "Marta Pradas-Juni and Hansmeier, {Nils R} and Link, {Jenny C} and Elena Schmidt and Larsen, {Bj{\o}rk Ditlev} and Paul Klemm and Nicola Meola and Hande Topel and Rute Loureiro and Ines Dhaouadi and Kiefer, {Christoph A} and Robin Schwarzer and Sajjad Khani and Matteo Oliverio and Motoharu Awazawa and Peter Frommolt and Joerg Heeren and Ludger Scheja and Markus Heine and Christoph Dieterich and Hildegard B{\"u}ning and Ling Yang and Haiming Cao and Jesus, {Dario F De} and Kulkarni, {Rohit N} and Branko Zevnik and Tr{\"o}der, {Simon E} and Uwe Knippschild and Edwards, {Peter A} and Lee, {Richard G} and Masayuki Yamamoto and Igor Ulitsky and Eduardo Fernandez-Rebollo and Vallim, {Thomas Q de Aguiar} and Jan-Wilhelm Kornfeld",
year = "2020",
doi = "10.1038/s41467-020-14323-y",
language = "English",
volume = "11",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "nature publishing group",

}

RIS

TY - JOUR

T1 - A MAFG-lncRNA axis links systemic nutrient abundance to hepatic glucose metabolism

AU - Pradas-Juni, Marta

AU - Hansmeier, Nils R

AU - Link, Jenny C

AU - Schmidt, Elena

AU - Larsen, Bjørk Ditlev

AU - Klemm, Paul

AU - Meola, Nicola

AU - Topel, Hande

AU - Loureiro, Rute

AU - Dhaouadi, Ines

AU - Kiefer, Christoph A

AU - Schwarzer, Robin

AU - Khani, Sajjad

AU - Oliverio, Matteo

AU - Awazawa, Motoharu

AU - Frommolt, Peter

AU - Heeren, Joerg

AU - Scheja, Ludger

AU - Heine, Markus

AU - Dieterich, Christoph

AU - Büning, Hildegard

AU - Yang, Ling

AU - Cao, Haiming

AU - Jesus, Dario F De

AU - Kulkarni, Rohit N

AU - Zevnik, Branko

AU - Tröder, Simon E

AU - Knippschild, Uwe

AU - Edwards, Peter A

AU - Lee, Richard G

AU - Yamamoto, Masayuki

AU - Ulitsky, Igor

AU - Fernandez-Rebollo, Eduardo

AU - Vallim, Thomas Q de Aguiar

AU - Kornfeld, Jan-Wilhelm

PY - 2020

Y1 - 2020

N2 - Obesity and type 2 diabetes mellitus are global emergencies and long noncoding RNAs (lncRNAs) are regulatory transcripts with elusive functions in metabolism. Here we show that a high fraction of lncRNAs, but not protein-coding mRNAs, are repressed during diet-induced obesity (DIO) and refeeding, whilst nutrient deprivation induced lncRNAs in mouse liver. Similarly, lncRNAs are lost in diabetic humans. LncRNA promoter analyses, global cistrome and gain-of-function analyses confirm that increased MAFG signaling during DIO curbs lncRNA expression. Silencing Mafg in mouse hepatocytes and obese mice elicits a fasting-like gene expression profile, improves glucose metabolism, de-represses lncRNAs and impairs mammalian target of rapamycin (mTOR) activation. We find that obesity-repressed LincIRS2 is controlled by MAFG and observe that genetic and RNAi-mediated LincIRS2 loss causes elevated blood glucose, insulin resistance and aberrant glucose output in lean mice. Taken together, we identify a MAFG-lncRNA axis controlling hepatic glucose metabolism in health and metabolic disease.

AB - Obesity and type 2 diabetes mellitus are global emergencies and long noncoding RNAs (lncRNAs) are regulatory transcripts with elusive functions in metabolism. Here we show that a high fraction of lncRNAs, but not protein-coding mRNAs, are repressed during diet-induced obesity (DIO) and refeeding, whilst nutrient deprivation induced lncRNAs in mouse liver. Similarly, lncRNAs are lost in diabetic humans. LncRNA promoter analyses, global cistrome and gain-of-function analyses confirm that increased MAFG signaling during DIO curbs lncRNA expression. Silencing Mafg in mouse hepatocytes and obese mice elicits a fasting-like gene expression profile, improves glucose metabolism, de-represses lncRNAs and impairs mammalian target of rapamycin (mTOR) activation. We find that obesity-repressed LincIRS2 is controlled by MAFG and observe that genetic and RNAi-mediated LincIRS2 loss causes elevated blood glucose, insulin resistance and aberrant glucose output in lean mice. Taken together, we identify a MAFG-lncRNA axis controlling hepatic glucose metabolism in health and metabolic disease.

KW - Aged

KW - Animals

KW - Diabetes Mellitus, Type 2/genetics

KW - Glucose/metabolism

KW - Humans

KW - Liver/metabolism

KW - MafG Transcription Factor/genetics

KW - Male

KW - Mice

KW - Middle Aged

KW - Obesity/genetics

KW - RNA, Long Noncoding/genetics

KW - RNA, Messenger/genetics

KW - Repressor Proteins/genetics

KW - TOR Serine-Threonine Kinases/genetics

U2 - 10.1038/s41467-020-14323-y

DO - 10.1038/s41467-020-14323-y

M3 - Journal article

C2 - 32005828

VL - 11

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

M1 - 644

ER -

ID: 389913596